Novel Method to Enhance Sternal Healing After Harvesting Bilateral Internal Thoracic Arteries With Use of Basic Fibroblast Growth Factor

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Atsushi Iwakura ◽  
Yasuhiko Tabata ◽  
Manabu Miyao ◽  
Makoto Ozeki ◽  
Nobushige Tamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Bypass Surgery ◽  
Active Form ◽  
Coronary Bypass ◽  
Coronary Bypass Surgery ◽  
Diabetic Patients ◽  
Fibroblast Growth ◽  
Group A

Background —Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) in coronary bypass surgery, especially for diabetic patients. We have reported that basic fibroblast growth factor (bFGF) enhanced regeneration of the skull. This study was designed to evaluate the effects of topical use of bFGF on sternal healing after removing the BITAs. Methods and Results —Forty-five Wistar rats were subjected to median sternotomy and were divided into 3 groups: 15 had the BITAs removed and had a bFGF sheet applied on the posterior table of the sternum (group A), 15 had just the BITAs removed (group B), and 15 had intact BITAs (group C). Five and 10 rats were euthanized 2 and 4 weeks after surgery, respectively, in all 3 groups. Peristernal blood flow, measured with use of a noncontact laser flowmeter, decreased after removal of the BITAs ( P <0.001). Four weeks after the surgery, PBF markedly increased only in group A (9.7±1.2, 6.5±0.6, and 8.2±0.5 mL · min −1 · 100 g −1 for groups A, B, and C, respectively; P <0.01 by ANOVA). Four weeks after surgery, the following findings were obtained only in group A: (1) nearly completely healed sternum filled with regenerated bone tissue, (2) marked angiogenesis around the sternum, and (3) osteoblasts in an active form around the edge of the sternum. Conclusions —The results suggest that use of the bFGF sheet offset the sternal ischemia and accelerated sternal healing. This method may help to decrease sternal necrosis in high-risk patients or allow extended use of BITAs in coronary bypass surgery.

scholarly journals Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery

Circulation ◽  
1999 ◽  
Vol 100 (18) ◽  
pp. 1865-1871 ◽  
Author(s):  
Roger J. Laham ◽  
Frank W. Sellke ◽  
Elazer R. Edelman ◽  
Justin D. Pearlman ◽  
J. Anthony Ware ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Bypass Surgery ◽  
Coronary Bypass ◽  
Coronary Bypass Surgery ◽  
Fibroblast Growth

Effects of Basic Fibroblast Growth Factor Administration on Vascular Changes in Wound Healing of Rat Palates

2008 ◽  
Vol 45 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Yuichiro Hata ◽  
Hitoshi Kawanabe ◽  
Yutaka Hisanaga ◽  
Kunihisa Taniguchi ◽  
Hiroyuki Ishikawa
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Scar Formation ◽  
Factor Group ◽  
Vascular Network ◽  
Fibroblast Growth ◽  
Vascular Changes ◽  
Group A

Objective: The purpose of this study was to investigate the vascular changes induced by mucoperiosteal denudation of rat palate and to elucidate the effects of basic fibroblast growth factor (bFGF) administration on the palatal vascular network in wound healing. Methods: A total of 117 male Wistar rats were used for the study on their 20th postnatal day. The animals were divided into three groups: a scar formation group, a basic fibroblast growth factor group, and a control group. The scar formation and basic fibroblast growth factor groups had lateral mucoperiosteum excised from the palate. In the basic fibroblast growth factor group, a solution of basic fibroblast growth factor was injected into the operated area 1 week after excision. At 6, 8, and 10 weeks postoperatively, palatal vascular changes were investigated by immunohistochemical staining and corrosion cast techniques. Results: Throughout the experimental period, there were significantly fewer vessels in the scar formation group than in the control and basic fibroblast growth factor groups. In the basic fibroblast growth factor group, the elongation of new vessels and capillary proliferation proceeded, and after 10 weeks a highly organized vascular network was established. The scar formation group showed few Volkmann's canals that were shrunken or closed, whereas the basic fibroblast growth factor group evidenced Volkmann's canals with arterioles or venules, as seen in the control. Conclusions: The results suggested that injection of basic fibroblast growth factor into palatal wounds improves the vascular supply to the operated mucosa and underlying bone during and after palatal wound healing, which may contribute to tissue remodeling of the palate during growth.

scholarly journals Oncogenic K-Ras and Basic Fibroblast Growth Factor Prevent FAS-Mediated Apoptosis in Fibroblasts through Activation of Mitogen-Activated Protein Kinase

2000 ◽  
Vol 148 (3) ◽  
pp. 557-566 ◽  
Author(s):  
Hirotaka Kazama ◽  
Shin Yonehara
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Active Form ◽  
Mitogen Activated Protein Kinase ◽  
Expression Cloning ◽  
Fibroblast Growth ◽  
Mitogen Activated Protein ◽  
Constitutively Active

By an expression cloning method using Fas-transgenic Balb3T3 cells, we tried to obtain inhibitory genes against Fas-mediated apoptosis and identified proto-oncogene c-K-ras. Transient expression of K-Ras mutants revealed that oncogenic mutant K-Ras (RasV12) strongly inhibited, whereas dominant-inhibitory mutant K-Ras (RasN17) enhanced, Fas-mediated apoptosis by inhibiting Fas-triggered activation of caspases without affecting an expression level of Fas. Among the target molecules of Ras, including Raf (mitogen-activated protein kinase kinase kinase [MAPKKK]), phosphatidylinositol 3 (PI-3) kinase, and Ral guanine nucleotide exchange factor (RalGDS), only the constitutively active form of Raf (Raf-CAAX) could inhibit Fas-mediated apoptosis. In addition, the constitutively active form of MAPKK (SDSE-MAPKK) suppressed Fas-mediated apoptosis, and MKP-1, a phosphatase specific for classical MAPK, canceled the protective activity of oncogenic K-Ras (K-RasV12), Raf-CAAX, and SDSE-MAPKK. Furthermore, physiological activation of Ras by basic fibroblast growth factor (bFGF) protected Fas-transgenic Balb3T3 cells from Fas-mediated apoptosis. bFGF protection was also dependent on the activation of the MAPK pathway through Ras. All the results indicate that the activation of MAPK through Ras inhibits Fas-mediated apoptosis in Balb3T3 cells, which may play a role in oncogenesis.

scholarly journals Gelatin Sheet Incorporating Basic Fibroblast Growth Factor Enhances Healing of Devascularized Sternum in Diabetic Rats

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Atsushi Iwakura ◽  
Yasuhiko Tabata ◽  
Nobushige Tamura ◽  
Kazuhiko Doi ◽  
Kazunobu Nishimura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Bone Mineral ◽  
Basic Fibroblast Growth Factor ◽  
Median Sternotomy ◽  
Diabetic Rats ◽  
Wound Complications ◽  
Diabetic Patients ◽  
Fibroblast Growth ◽  
Mineral Density

Background Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) after coronary bypass surgery in diabetic patients. We have reported that a gelatin sheet that incorporates basic fibroblast growth factor (bFGF) accelerates sternal healing after BITA removal in normal rats. This study evaluated the effects of the above method for sternal healing in diabetic animals. Methods and Results Diabetic Wistar rats with blood glucose levels >400 mg/dL and body-weight loss >20 g were established by a single intravenous injection of streptozotocin (55 mg/kg). After median sternotomy and BITA removal, 16 diabetic rats received either a gelatin sheet that incorporated bFGF (100 μg/sheet) on the posterior table of the sternum (FGF group, n=9) or no gelatin sheet (control, n=7). Peristernal blood flow, as measured by a noncontact laser Doppler 4 weeks after surgery in the FGF group, recovered to the preoperative level (106±10% versus 82±9%, P <0.01), and marked angiogenesis was also observed around the sternum in the FGF group (30.5±3.2 versus 15.8±2.7 vessels/unit area, P <0.01). Deep sternal wound complications developed in 5 control rats but only in 1 rat in the FGF group ( P <0.05). In the FGF group, histological examination showed improved sternal healing (excellent in 6 rats and slow/poor healing in 3). Bone mineral content as assessed by dual-energy x-ray absorptometry was greater in the FGF group (75.9±18.1 versus 48.9±10.7 mg, P <0.05). Bone mineral density of the sternum was similar between the 2 groups. Conclusions A gelatin sheet that incorporates bFGF may offset sternal ischemia and accelerate sternal bone regeneration and healing, even in diabetic patients.

Properly Oriented Heparin−Decasaccharide-Induced Dimers Are the Biologically Active Form of Basic Fibroblast Growth Factor

Biochemistry ◽  
1997 ◽  
Vol 36 (25) ◽  
pp. 7936-7936
Author(s):  
Franklin J. Moy ◽  
Michal Safran ◽  
Andrew P. Seddon ◽  
Doug Kitchen ◽  
Peter Böhlen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Active Form ◽  
Biologically Active ◽  
Fibroblast Growth

Properly Oriented Heparin−Decasaccharide-Induced Dimers Are the Biologically Active Form of Basic Fibroblast Growth Factor†,‡

Biochemistry ◽  
1997 ◽  
Vol 36 (16) ◽  
pp. 4782-4791 ◽  
Author(s):  
Franklin J. Moy ◽  
Michal Safran ◽  
Andrew P. Seddon ◽  
Doug Kitchen ◽  
Peter Böhlen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Active Form ◽  
Biologically Active ◽  
Fibroblast Growth
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